Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing
Abstract
:1. Introduction
2. Results
2.1. Chokepoint Proteins Analysis
2.2. Metabolic Pathway Analysis
2.3. Essential Proteins Analysis
2.4. The In Vitro Anti-Helicobacter Activity of Selected Ligands
3. Discussion
4. Materials and Methods
4.1. Analysis of Chokepoint Proteins and Metabolic Pathway Proteins
4.1.1. Retrieval of Chokepoint Proteins of H. pylori
4.1.2. Retrieval of Proteins Involved in H. pylori Metabolic Pathways
4.1.3. Non-Homology Analysis to Human Proteins
4.1.4. Essentiality Analysis
4.1.5. Prediction of Sub-Cellular Localization
4.1.6. Conservation in H. pylori
4.1.7. Non-Homology to Proteome of Common Gut Flora Organisms
4.1.8. Druggability Analysis
4.1.9. Checking for Broad-Spectrum Targeting
4.2. Essential Proteins Analysis
4.3. Determination of MIC
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Target | Protein Name | App | Pathway | Similarity to Common Pathogen | Possible Ligands | Ligand Drugbank Accession Number |
---|---|---|---|---|---|---|
AroE | Shikimate dehydrogenase | PW EP | Phenylalanine, tyrosine, and tryptophan biosynthesis | Mostly 80–200 | 1,4-Dithiothreitol | DB04447 |
Nicotinamide adenine dinucleotide phosphate | DB03461 | |||||
2′-Monophosphoadenosine-5′-diphosphate | DB02363 | |||||
AroQ | 3-dehydroquinate dehydratase | CP PW EP | Phenylalanine, tyrosine, and tryptophan biosynthesis | Mostly 80–200 | 3-Dehydroquinic Acid | DB03868 |
N-(1,4-dihydro-5H-tetrazol-5-ylidene)-9-oxo-9H-xanthene-2-sulfonamide | DB04698 | |||||
2,3-Anhydro-quinic acid | DB02801 | |||||
3-Hydroxyimino quinic acid | DB03739 | |||||
2-Anhydro-3-fluoro-quinic acid | DB02786 | |||||
3-Dehydroshikimate | DB04347 | |||||
1,3,4-Trihydroxy-5-(3-phenoxypropyl)-cyclohexane-1-carboxylic acid | DB04656 | |||||
(1s,4s,5s)-1,4,5-Trihydroxy-3-[3-(phenylthio)phenyl]cyclohex-2-ene-1-carboxylic acid | DB08485 | |||||
CheY | chemotaxis protein | PW EP | Two-component system and bacterial chemotaxis | >200 | S-Methyl Phosphocysteine | DB02461 |
(S)-Aspartimide | DB03487 | |||||
Aspartate Beryllium Trifluoride | DB04156 | |||||
Adenosine-5′-Rp-Alpha-Thio-Triphosphate | DB02355 | |||||
alpha,beta-Methyleneadenosine 5′-triphosphate | DB02596 | |||||
2-Hydroxyestradiol | DB07706 | |||||
Guanosine-5′-Monophosphate | DB01972 | |||||
Phosphoaspartate | DB01857 | |||||
CmoA | Carboxy-S-adenosyl-L-methionine synthase | CP EP | 5-(methoxycarbonylmethoxy)uridine biosynthesis | >200 | S-Adenosyl-L-Homoselenocysteine | DB03423 |
DapB | 4-hydroxy-tetrahydrodipicolinate reductase | CP PW EP | Lysine biosynthesis | >200 | 3-Acetylpyridine Adenine Dinucleotide | DB03363 |
Dipicolinic acid | DB04267 | |||||
Ddl | D-alanine-D-alanine ligase | CP PW EP | D-alanine metabolism and Peptidoglycan biosynthesis | >200 | 3-Chloro-2,2-dimethyl-n-[4-(trifluoromethyl)phenyl]propanamide | DB07805 |
DnaN | DNA polymerase III subunit β | PW EP | DNA replication, Mismatch repair, and Homologous recombination | >200 | [(5R)-5-(2,3-dibromo-5-ethoxy-4-hydroxybenzyl)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid | DB06998 |
HP0405 | Hypothetical protein 0405 | EP | NA | >200 | Selenocysteine | DB02345 |
S-Mercaptocysteine | DB02761 | |||||
S-Selanyl Cysteine | DB03049 | |||||
L-2-amino-3-butynoic acid | DB04217 | |||||
3′-O-N-Octanoyl-a-D-Glucopyranosyl-B-D-Fructofuranoside | DB02346 | |||||
IspA | Geranyl diphosphate synthase | CP PW EP | Terpenoid backbone biosynthesis | >200 | Pyrophosphoric acid | DB04160 |
Isopentyl Pyrophosphate | DB02508 | |||||
Dimethylallyl S-Thiolodiphosphate | DB02270 | |||||
LacA/ Rpi | Ribose-5-phosphate isomerase B | PW EP | Pentose phosphate pathway, Fructose and mannose metabolism | 80–200 | 2′-Monophosphoadenosine-5′-Diphosphate | DB02363 |
LpxA | Acyl-[acyl-carrier-protein]—UDP-N-acetylglucosamine O-acyltransferase | PW EP | Lipopolysaccharide biosynthesis | >200 | D-tartaric acid | DB01694 |
2-Hydroxymethyl-6-octylsulfanyl-tetrahydro-pyran-3,4,5-triol | DB08558 | |||||
4-Chloro-N-(3-methoxypropyl)-N-[(3S)-1-(2-phenylethyl)piperidin-3-yl]benzamide | DB08344 | |||||
PanD | Aspartate 1-decarboxylase proenzyme | PW EP | β-alanine metabolism | 80–200 | Malonic acid | DB02175 |
S-oxy-L-cysteine | DB03382 | |||||
RibC | Riboflavin synthase | CP PW EP | Riboflavin metabolism | >200 | Citric acid | DB04272 |
Flavin mononucleotide | DB03247 | |||||
Lumichrome | DB04345 | |||||
RplE | 50S ribosomal subunit L5 | PW EP | Ribosome | >200 | (S)-3-phenyllactic acid | DB02494 |
RpsF | 30S ribosomal subunit S6 | PW EP | Ribosome | 80–200 | 2-Methylthio-n6-isopentenyl-adenosine-5′-monophosphate | DB08185 |
RpsJ | 30S ribosomal subunit S10 | PW EP | Ribosome | 80–200 | 2-Methylthio-n6-isopentenyl-adenosine-5′-monophosphate | DB08185 |
TrbB/VirB11_2 | Type IV secretion system ATPase | PW EP | Bacterial secretion system Epithelial cell signaling | Mostly 80–200 | 2′-Monophosphoadenosine-5′-Diphosphate | DB02363 |
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Ibrahim, K.A.; Helmy, O.M.; Kashef, M.T.; Elkhamissy, T.R.; Ramadan, M.A. Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing. Pathogens 2020, 9, 747. https://doi.org/10.3390/pathogens9090747
Ibrahim KA, Helmy OM, Kashef MT, Elkhamissy TR, Ramadan MA. Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing. Pathogens. 2020; 9(9):747. https://doi.org/10.3390/pathogens9090747
Chicago/Turabian StyleIbrahim, Kareem A., Omneya M. Helmy, Mona T. Kashef, Tharwat R. Elkhamissy, and Mohammed A. Ramadan. 2020. "Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing" Pathogens 9, no. 9: 747. https://doi.org/10.3390/pathogens9090747